Enclosed is my response to the questions posed:
1)what should the PCP do?
2)what might have happened?
3) what are the consequences of the disease and treatment?
My last helpful textbook was “Clinical Microbiology Made Ridiculously Simple” a million years ago, so bear with me here.
The CDC as well as various assorted sources say that Entamoeba Hartmanni is a nonpathogenic, commensal organism that does not require treatment. It used to be referred to as “the small race” or minuta, as it looked very similar to Entamoeba histolytica but is a lot smaller.
Transmission is via cysts in the stool, so she likely contracted it through contaminated food, water, or fomites.
Versus histolytica, it seems to be called “nonpathogenic” because it doesn’t invade surrounding structures.
1) In terms of what you should do- my educated guess would be nothing but maintain good hand hygeine. It’s not supposed to be harmful to the host. *
2) For what might have happened- the PCP could have easily prescribed metronidazole, iodoquinol, or chloroquine. All of these are treatments for intestinal amoebiasis.
3) Side effects of all of them are diarrhea.
More serious potential side effects for metronidazole would be aseptic meningitis and optic neuropathy, which are associated with higher doses of the drug.
For iodoquinol, it can cause alterations in thyroid gland function, and is also associated with optic neuritis.
For chloroquine, retinal damage.
*I have no idea why the amebiasis is helping with her chronic constipation- as it shouldn’t be doing anything to the intestinal wall. As far as I could find out, it doesn’t really have an interaction with it like histolytica does. So perhaps there was a diagnostic error as hartmanni and histolytica are morphologically similar, and a PCR test might be needed if this was diagnosed only with microscopy.
So maybe she does have histolytica, and the damage to the intestinal wall is “helping” with her constipation as she would ordinarily have diarrhea with blood and mucus instead. So I wonder, what exactly is the quality of her new normal stools?
Some people are asymptomatic, but otherwise, invasion of the intestinal wall can cause a perforation and peritonitis. Toxic megacolon is also possible and has high mortality. Granulation tissue can occur at the sites of healing amoebic ulcers and cause an intestinal mass (ameboma). Fibrosis can also cause intestinal stricture.
Histolytica can then invade distant sites, the most common being the liver- and the subsequent necrosis of the site can cause an amoebic abscess. Rupture of the liver abscess and erosion of the diaphragm can lead to pleural effusion and pleural abscess. You can also have a pericardial amebiasis with signs typical of pericarditis and congestive heart failure. Tamponade physiology and shock can also occur.
Cerebral amebiasis is particularly bad.
This answer turned out to be a lot longer than expected.
I’m a long-time lurker, first time answerer. Hope it was a good try. I’d love to be in the running for your book.
Still snowing in Rochester-NY,
PS: how did you guys decided on getting Ronald Jenkees? Love this guy’s music, but did not expect to see him composing your intro music.
Hunter’s Tropical Medicine and Emerging Infectious Diseases. 9th ed.
Hi TWiP Experts,
At first, when I heard “Punta Cana” I immediately thought of the two tourists that were infected with hookworm last year when walking barefoot on the beach, but this case doesn’t sound so easy.
I started by listing the notes that Dr. Griffin provided:
- Travel to Punta Cana.
- Resolution of chronic constipation after a few weeks.
- Entamoeba hartmanni isolated.
Several Caribbean parasites initially come to mind, including: Schistosoma mansoni, Strongyloides stercoralis, hookworm and the usual intestinal suspects (Giardia etc).
Entamoeba hartmani is typically non-pathogenic in healthy people, so I found it odd that this was the only parasite that was isolated.
As for the resolution of the constipation, I didn’t, and still don’t have a good explanation. I found an article published in Frontiers of Cellular Neuroscience titled “Gastrointestinal Parasites and the Neural Control of Gut Functions” that discusses the impact that some parasitic infections have on gut motility. Perhaps this woman’s parasitic infection has improved her gut motility and this has temporarily resolved her chronic constipation?
I think that it would be beneficial for the doctor to ask the patient to submit a second sample. It is possible that a pathogenic organism was missed. Intestinal non-pathogens sometimes keep the pathogenic organisms company.
I noticed that the resolution of the constipation began after a few weeks which makes me lean towards some kind of soil transmitted helminth rather than an amoeba. If this is the case, and the patient is infected with something like Strongyloides stercoralis, the constipation will likely return in addition to nutrient absorption complications.
I am looking forward to hearing the rest of this case on the next episode.
Dear Giardians of the Galaxy,
I love this case because it reminds me of the numerous stories I’ve heard of people waking up one day having overcome problems they’ve had in the past with no obvious reason why (myself included). I don’t have a great deal of medical knowledge but I’ll do my best to propose some ideas.
1. E. hartmanni is pretty well ubiquitously considered a commensal that is incapable of causing disease, but I found a very recent paper that suggests it may be associated with chronic mild diarrhoea (https://tropmedhealth.biomedcentral.com/articles/10.1186/s41182-018-0132-7#Bib1). Perhaps the combination of pre-existing constipation and something that causes chronic mild diarrhoea leaves the patient with regular bowel movements. If this is the case, I would suggest no treatment, unless the diarrhoea becomes a bigger issue than the constipation was. I like this idea most, because I think there are a huge number of pathogens that cause common or complex symptoms whose disease burden we either under appreciate or is currently undiscovered, and recognition of this puts us a step closer to helping the people affected by them.
2. E. hartmanni apparently looks very similar to E. histolytica, perhaps this is causing a similar situation to what i described above but was misdiagnosed as E. hartmanni. This seems unlikely because she has no described symptoms that would fit E. histolytica and I assume in the USA this would not be diagnosed by stool microscopy because of the other potentially confounding amoebae.
3. The diagnosis has nothing to do with the resolution of her constipation but is simply a coincidence. It isn’t clear whether she was previously infected with E. hartmanni and given that it is common pretty much worldwide, according to my brief reading, I don’t think we can be overly confident that she acquired it in the DR.
4 (and most likely). It’s something completely different that I haven’t thought of
Something I read while looking through the E. hartmanni literature was the extreme prevalence of parasitic and neglected diseases in Australian Aboriginal children. I also heard a presentation once that said remote Australian Aboriginals are the population with the world’s highest rates of trachoma. While this both shocks and saddens me, it reminds me of a discussion on TWiP many moons ago with Peter Hotez where he discussed the under appreciated burden of NTDs among the poor in rich countries. Perhaps this topic deserves revisiting, is the prevalence of NTDs in richer countries better studied, appreciated or understood than it was in 2011? I would love to hear what the TWiP team have to say about this.
It’s the first day of ‘autumn’ here in sometimes too sunny Adelaide, South Australia. I put autumn in inverted commas because it is currently 40 degrees Celsius and I don’t think that fits anybody’s idea of an autumn day. Thank you for all the wonderful work.
Keep calm and TWiP on,
PhD Candidate – Malaria Biology Lab (Wilson Lab)
Research Centre for Infectious Diseases
School of Biological Sciences
The University of Adelaide
You’ve given us quite a hard one, to make up for the previous two softballs. That’s not a complaint – it’s fun to have something you can really sink your teeth into.
This case is made even more difficult by the fact that we don’t know what caused the chronic constipation, let alone what cured it. Perhaps the condition that causes constipation and some parasite that causes loose stools are balancing out somehow, leading to normal-seeming bowel movements? Or, was the condition actually corrected by whatever happened in the Dominican? Given the lack of solid (heh) information, we are making a tree of several options.
- The softer stools are caused by E. hartmanni.
- The softer stools are not caused by E. hartmanni, but are caused by something she acquired at the same time in the same way (probably in the water), making E. hartmanni an indicator of sorts.
- They are caused by a eukaryotic parasite.
- They are caused by something other than a eukaryotic parasite.
- The softer stools are caused by something completely unrelated, and the E. hartmanni is a red herring.
i), ii): see above.
We are mainly considering organisms which cause loose stools/diarrhea, on the grounds that this patient has what are loose stools by her standards.
Possibility a) has some merit. Many organisms cause no symptoms in the vast majority of the population, but in a few rare patients do cause GI symptoms. Given that this patient has a history of GI trouble, she may be at risk for membership in that group. While cursory searches on the internet and in Parasitic Diseases reveal no instances of diarrheal disease or even softened stools caused by E. hartmanni, that doesn’t mean it’s impossible. There is infinite variation in biology, after all. If, indeed, this is the case, there is probably no reason to treat the patient at all. The organism is causing no apparent harm, and is in fact beneficial, though of course the situation should be monitored.
Possibility b)-i) (other water-borne parasite) brings up several options – and the same objection to most of them. There are numerous diarrhea-causing parasites in the water in the Dominican Republic. However, her stool was examined, and one protist was spotted; most of these other options should have been spotted as well.
There is a laundry list of protozoa which cause diarrhea, or can cause diarrhea under some circumstances. Cystoisospora belli, Cyclospora cayetanensis, Blastocystis hominis, Dientamoeba fragilis, Balantidium coli, and last TWiP’s villain, Giardia lamblia. There is fairly little to choose between most of these, and if indeed any of these are causing the patient’s symptoms, it is a fairly atypical presentation. We can probably eliminate Giardia, though; not only was it the solution last time, but it has very distinct symptoms that are not present in this patient. (This is disappointing, as it’s classically hard to spot in a stool sample.)
Going through those above:
Cystoisospora belli causes secretory diarrhea, i.e. water loss from the lower intestine. This could theoretically be loosening the patient’s stools, if her constipation was caused by dehydration. However, there are two big objections – the patient has suffered from constipation for years, and if it was merely dehydration causing it, there are several products that can help draw water from the intestines and soften stools, and she probably would have tried these. Secondly, she is probably not immunocompromised, and C. belli mainly infects the immunocompromised.
Cyclospora cayetanensis – mostly the same as the above. While an immunocompetent person may catch this, it will probably clear up quickly, making it less likely to cause “symptoms” for so long (we assume several weeks, at least).
Blastocystis hominis is very common worldwide, and is usually not pathogenic, or not unambiguously so. It can cause GI symptoms, but isn’t associated with immunocompromised patients in particular, and is generally very mysterious. That, at least, fits with this case.
Dientamoeba fragilis also causes diarrhea… sometimes, in some patients, and, like B. hominis, it isn’t always clear when and why. As an added bonus, it’s hard to detect, being fragile, which would explain that bit, at least.
Balantidium coli is known to cause chronic infection, which fits with this case. However, it causes dysentery, which doesn’t. It also tends to cause much more severe disease.
And, finally, a tinfoil-hat option: She actually has E. histolytica, not E. hartmanni. While the story normally goes that E. hartmanni is confused for E. histolytica by an inexperienced diagnostician, leading to unnecessary treatment, it could theoretically happen the other way around. However, that is unlikely for many reasons. For one, the examiner should be looking for the disease-causing organisms, and would have it on their mind. It would be truly spectacular incompetence to brush off the harmful amoeba as the morphologically similar harmless one. Furthermore, E. histolytica causes dysentery, which was not noticed in this case.
The treatments for these protozoans are very different, so further diagnostics are needed. Since examining the stool didn’t detect any of these, we would use PCR.
Next, we go to possibility b)-ii) – a water-borne pathogen (?) that is not a eukaryotic parasite. The main cause of traveler’s diarrhea is E. coli, and there are plenty of other bacteria as well. However, we would not expect these to last so long at equilibrium, especially after coming back.
Another option: her constipation was caused by some irregularity in her gut flora. In that case, this patient unwittingly drank contaminated water and by sheer fluke, instead of picking up any of the many, many nasty beasties that are transmissible by that route she got a commensal amoeba and some of the normal gut flora she was chronically lacking. That would be a case for TWiM, but since there is a eukaryote involved, perhaps Daniel was just feeling more evil than usual. It makes a good story, but is it likely? Not really. Aside from the low probability, adults don’t really add to their gut flora in the long term. Newcomers are usually only present transiently before dying off or being killed off by the immune system.
Next, we move on to possibility c)-i): completely unrelated parasite.
The patient was in the Dominican Republic, and there are GI symptoms, if you can call them symptoms. Strongyloides has to be on the list. However, it’s very, very unlikely to be asymptomatic except for correcting the constipation, and if the diagnostician noticed the E. hartmanni and didn’t notice this, they are even more incompetent than in the E. histolytica hypothesis.
There are plenty of other helminths that can cause diarrhea, and many are in the Dominican Republic. Some examples: Trichuris (no), hookworm (…no. Just no), Trichinella (hi Dickson! Not this either). These all cause many symptoms, usually much more obvious than very slightly loose stools, would have been spotted in the stool exam, and the whole thing is altogether too far-fetched.
However: it is known that some helminth infections can cure certain kinds of autoimmune disease, including some forms of inflammatory bowel syndrome. In fact, as discussed in several TWiP episodes, some sufferers will even intentionally infect themselves with helminths. Could that have been the cause of her chronic constipation? Could she have acquired a helminth in the Dominican, and unintentionally given herself the same treatment? It’s an intriguing possibility. However, the objection that a helminth should have been diagnosed by the stool exam still stands.
Finally, we get to possibility c)-ii), which translates to “we throw up our hands.” Could she have radically changed her diet after the Dominican trip? Could it be psychosomatic? Surely you wouldn’t do that to us.
At this point, we stop. This is getting quite silly.
We apologize for the enormous wall of text, but you rather asked for it with that bizarre and intriguing case. We don’t really have a solution. Caitlin’s gut instinct, no pun intended, is Blastocystis hominis. Carrie (who would have made that pun intentionally if Caitlin hadn’t got there first) would really love the accidental foecal bacteriotherapy to be true, but is going to go with E. hartmanni actually causing this, as being slightly less improbable.
This letter is a product of the notorious transatlantic duo: Carrie, from Newcastle-Upon-Tyne, England, and Caitlin, in Seattle. We can’t agree on which one of us gets the book if we win, so please rip it in half à la King Solomon and send one-half to each of us. In the future, we’ll each diagnose the cases that are in our own section.
Temperature is back to freezing in Athens, GA, so it looks like we have a chance at ANOTHER snow-less winter.
For this case (and depending on the ultimate diagnosis) the infection seems to be unusually fortuitous. My immediate thought is that an infection normally associated with loose stools may have brought some regularity to the patient, however precarious that balance might be.
Since E. hartmanni is usually non-pathogenic, the intestinal changes experienced by the patient are very possibly unrelated. This amoeba may only be an indicator that she has been exposed to fecally contaminated food or water and she should be retested for parasites that might have been missed, including Giardia and Cryptosporidium. Another possibility is Strongyloides, which develops quickly enough to induce intestinal changes in the time-frame seen here, and frequently evades detection on fecal exam; in this case the physician may order a serological test. In any event, a follow-up fecal exam may reveal parasites that are already affecting the gut, but haven’t yet reached patency.
Kleptoparasitism and the stercoraceous souvenir aka the colonic stowaway from Hispaniola.
30 y/o woman, trip to Dominican Republic. Patient’s history of constipation, present since childhood, has resolved upon return from her Caribbean holiday. Routine wellness visit to her long-time physician seemed to stimulate a thought which resulted in a lab finding of Entamoeba hartmanii. (The provenance of this eponymous Entamoeba is traced in the endnotes). Is this physician engaging in fecal relativism, where a restoration to ‘normal’ in a chronically constipated patient is interpreted as a diarrheal equivalent? I admit that the logic of this possibility could be described as tortured. Nevertheless, this story is a reassuring counterpoint to the standard narrative of cruise ship diarrhea and the dreaded ‘tourista or Montezuma’s revenge’, if anyone even uses these questionable expression anymore. Our case is a very arresting anecdote. It holds promise. It has the allure of tropical travel, leisure, and an intimate if not occult association resulting in an unexpected resolution of a disturbing condition by a lowly actor formerly considered a parasite.
Despite my aversion to medical metaphors, this case, with its tantalizing vagueness, has spawned a cascade of topics that can be best described as constipating the mind. The historical sweep of our case encompasses protozoology’s golden age starring Hartmann, Schaudinn and Geimsa as well as the frontiers of the gut microbiome. We may also mention so-called ‘late capitalism’ wherein previously valueless human feces has become commodified (see Sunday March 3 New York Times feature on fecal transplantation). The NYT account of a fecal transplant imbroglio recalls Part III, Chapter V of Gulliver’s Travels: The Voyage to Laputa: The most ancient student of the academy….his employment…was an operation to reduce human excrement to its original food, by separating the several parts, removing the tincture which it receives from the gall, making the odour exhale, and scumming off the saliva. He had a weekly allowance, from the society, of a vessel filled with human ordure, about the bigness of a Bristol barrel. The intersection of Bristol here and the Bristol Stool Form Scale shall remain unremarked upon.
One might say that our patient had an inadvertent micro-fecal transplant while traveling. Though Entamoeba hartmanni was recovered on return the the United States, we do not know if she had this commensal in her gut prior to traveling. It is also unknown what other bacterial, fungal or protozoan commensals she may have acquired during her trip. We simply have a seductive scenario of a person with a nettlesome chronic disease who has been apparently ‘cured’ through travel, with the lowly E hartmanni serving as a MacGuffin or red herring. There are some very large lacunae in this story, and making the assumption that E. hartmanni is the agent of her relief is impermissible. Nevertheless, this parable provides a good excuse to meditate on the gut microbiome.
The bacterial gut microbiome has had a head-start on the so-called eukaryome (some say eukaryotome) due in part to the earlier availability of 16S rRNA assays. Newer 18S rRNA assays and other techniques have begun to elucidate the fungi, protozoa, and helminths that live within us. Studies on commensal eukaryotes in the gut are at a very early stage however. Classification of gut protozoa are being reassessed as to who is what: a parasite, pathobiont, symbiont, commensal, mutualist etc. Greater gut microbiome diversity is now believed to be beneficial. There is the ‘hygiene hypothesis’ and the ‘old-friends hypothesis’ that postulate that the decline in microbial contact in infancy and childhood has led to the development of allergic and autoimmune diseases. The ol’ nostalgie de la boue. I could find nothing in the medical literature to suggest that protozoa could be employed in the treatment of constipation but a reference is included that claims that fecal transplantation was beneficial. Population surveys show relatively low levels of E. hartmanni colonization, in the 3% range (see references). There are a few case reports that try to tarnish the reputation of E hartmanni by associating it with reactive arthritis or mild diarrhea. Regarding our patient, it is possible that her new ‘old-friends’, E hartmanni and probably others, have had salutary effects on gut motility, mucus production, production of local neuroendocrine mediators such as serotonin, gut immune and inflammasome function. Something got things moving again. Leung (REF) has a poetic way of describing this whole situation “…parasites can serve as ecosystem engineers for gut microbes by altering the physical landscape in which they reside.”
I can only hope that our patient is not in a honeymoon period with her new companion and that there will be no return to costiveness. Also, there is perhaps a deeper meaning to the 70s expression ‘get your shit together’ : By appreciating our inner universe and the likely benefits of migrants we might come to a greater understanding —of biology and whatever other metaphor you like.
Thanking TWiP triumvirs (or do you say triumviri?)
ENDNOTES, REFERENCES AND A TERMINAL CURIOSITY
my comments are italicized
¶ ENTAMOEBA REFERENCES
Diagnostic Medical Parasitology, Garcia, Lynne Shore. 2007 (5th edition) ASM Press. “Until 1957 E hartmanni was considered a ‘small race of E histolytica’. E hartmanni cysts=5-10 mm, trophozoites=8-10 mm. Compare E histolytica: cysts=10-20 mm , trophozoites=15-20 mm (can be as large as 60mm diameter). Generally regarded as non-pathogenic and it is unnecessary to treat.”
Amebiasis (book)—-Bhattacharya A, Campbell D, Cantellano M Espinosa World Scientific, Feb 28, 2000
“Entamoeba hartmanni: In 1912, von Prowazek had described an organism he named Entamoeba hartmanni. This amoeba was morphologically similar to E. Histolytica and also produced cysts with four nuclei but was smaller. Dobell deemed it to be a synonym as the size range of E Hartmanni overlapped with that of E histolytica. His view as widely accepted and remained so until the mid 1950s…when Burrows demonstrated….two distinct mean sizes….and recently phylogenetic analysis has shown that the tow are not very closely related.”
Entamoeba Species in South Africa: Correlations With the Host Microbiome, Parasite Burdens, and First Description of Entamoeba bangladeshi Outside of Asia, Renay Ngobeni, JID 2017:216 (15 December)
Stool survey of 484 persons, 140 of whom tested positive (by multiplex qPCR). E hartmanni was positive in 13 (2.7%).
Repertory of eukaryotes (eukaryome) in the human gastrointestinal tract: taxonomy and detection methods, Hamad, I., Raoult, D., & Bittar, F. (2015). Parasite Immunology, 38(1), 12–36.
referenced by Chabé. Massive table of eukaryotic organisms which have been described to inhabit the human gutA thorough review of the types of eukaryotes found in the human gut biome -(the human gut eukaryome) and the methods employed in their detection.
“Comprehensive analysis of the eukaryotic component of the human gut revealed the presence of more than 15 different protistan genera belonging to diverse groups such as amoebozoans, flagellates amitochondriate protozoa, ciliates, apicomplexans and stramenopiles that are known to parasitize or commensalize the intestinal tract of humans.”
Frequency and molecular characterisation of Entamoeba histolytica, Entamoeba dispar, Entamoeba moshkovskii, and Entamoeba hartmanni in the context of water scarcity in northeastern Brazil, Deiviane Aparecida Calegar, Mem Inst Oswaldo Cruz. 2016 Feb; 111(2): 114–119. OPEN ACCESS
“E. histolytica, E. dispar, E. moshkovskii, and E. hartmanni were identified by nested-polymerase chain reaction (PCR). The overall prevalence of infection was 22/213 (10.3%). —This 10% figure was broken down by species….=The species distribution was as follows: 57.1% to E. dispar, 23.8% to E. histolytica, 14.3% toE. histolytica and E. dispar, and 4.8% E. dispar and E. hartmanni…..In addition, differential diagnosis should also consider the nonpathogenic species E. hartmanni, which can be distinguished from E. histolytica by its small cyst size (5-10 µm in diameter) ….More recently, dysentery and extraintestinal disease have been proposed to be potentially associated with E. dispar and E. moshkovskii (Parija & Khairnar 2005, Costa et al. 2010). These findings complicated our understanding of the pathogenic behaviour and public health importance of indistinguishable E. histolytica/E. dispar/E. moshkovskii complex and E. hartmanni parasites (Oliveira et al. 2015).”
Molecular Epidemiology of Entamoeba: First Description of Entamoeba moshkovskii in a Rural Area from Central Colombia, López MC et al. (2015) PLoS ONE 10(10)
“Amoebiasis is the parasitism caused by Entamoeba histolytica, the only pathogenic species among the amoebas that inhabit in the human digestive tract and other organs. It is one of the most prevalent parasitic diseases worldwide, particularly in developing countries where sanitation is insufficient. The genus Entamoeba includes six species: E. histolytica, E. dispar, E. moshkovskii, E. bangladeshi,E. poleki, E. coli and E. hartmanni. The first three species are morphologically similar but with different biochemical and genetic features. Previously, it was considered that about 500 million people were infected with E. histolytica worldwide. However, this frequency is overestimated due to the use of light microscopy instead of molecular tools able to differentiate the species. Asymptomatic presentation is the most common clinical form of amoebiasis (around 80–90% of the cases) and might be caused by three independent species: The pathogenic amoeba E. histolytica, E. disparconsidered as a commensal and E. moshkovskii in which the pathogenic potential is still under discussion. This premise reflects the need to understand the molecular epidemiology of these species in endemic countries. the reference is a 1997 WHO derived citation…”
An Annotated Checklist of the Human and Animal Entamoeba (Amoebida: Endamoebidae) Species- A Review Article, Hossein HOOSHYAR, et al, Iran J Parasitol. 2015 Apr-Jun; 10(2): 146–156. OPEN ACCESS
Like Casubon’s Codex of all Mythologies….
3-Entamoeba hartmanni (Von Prowazek, 1912)
- Synonyms: Small race E. histolytica, Entamoeba minuta (Woodeock & Penfold, 1916), Entamoeba minutissima (Brug, 1918), Entamoeba tenuis (Kuenen & Swellengrebel, 1917)
- Hosts: Human
- Habitat: Colon and caecum, large intestine
- Pathogenicity: None
- Distribution: Worldwide
LUMINEXW: a new technology for the simultaneous identification of five Entamoeba spp. commonly found in human stools, Helena Lúcia Carneiro Santos et al, Santos et al. Parasites & Vectors 2013, 6:69, OPEN ACCESS
Good overview of newer method to reliably separate various Entamoeba species, especially E histolytica vs E dispar.
Variation in African Gut Microbiota Is Strongly Correlated with Colonization by Entamoeba and Subsistence. Elise R. Morton et al, PLOS Genetics,11(11): November 30, 2015, OPEN ACCESS
Last author: Laure Ségurel, from Columbia University Dept Biol Sciences—maybe TWiP professors know her…. Study looked at E. histolytica and E dispar… 64 subjects…(the majority of subjects had asymptomatic carriage). Demonstrated reproducible and characteristic microbiome changes in gut bacteria in Entamoeba colonized people. The authors have several intriguing speculations about the inter-relationship of bacteria, protozoa and the immune system in the gut. They cite several studies which make links with similar microbiome changes in various disease states (inflammatory bowel disease and rheumatoid arthritis). E hartmanni and other Entamoeba species are not mentioned…. quote from the article: “Interestingly, we found that the majority of specific taxa for which abundance significantly correlated with the presence of Entamoeba share the common feature that they have been highlighted for their potential role as signatures of inflammation-related diseases. For example, Clostridiales Ruminococcaceae, the second most important taxon in the RFC model, significantly more abundant in Ent+ individuals, has been found to be underrepresented in individuals suffering from Crohn’s Disease and Ulcerative Colitis . Likewise, a decreased prevalence of Prevotella copri and Fusobacteria, as observed in Ent+ individuals, was recently shown to be negatively correlated with rheumatoid arthritis and incidence of colorectal cancer, respectively. Although speculative, these relationships suggest a potential link between gut parasites, gut bacteria, and host inflammation.”
¶ THROWIN’ SHADE ON E. HARTMANNI
Entamoeba hartmanni: a new causative agent in the pathogenesis of reactive arthritis? M. Schirmer et al, Rheumatol Int (1998) 18: 37–38
Basically a speculative case report. Patient presumably acquired E hartmanni in Madagascar, developed an arthritic syndrome upon return to Austria, and was clinically improved after metronidazole treatment. Such observations are problematic since there is seldom pre-morbid data concerning a patient’s microbiome/eukaryome.
Possible pathogenicity of commensal Entamoeba hartmanni revealed by molecular screening of healthy school children in Indonesia, Matsumura T et al. Trop Med Health. 2019;47:7. Published 2019 Jan 15.OPEN ACCESS
n=144 (“healthy population”), 31% positive for E. hartmanni (molecular screening). They associated this with mild diarrhea. A speculative and small case series.
¶ GUT MICROBIOME WITH AN EMPHASIS ON EUKARYOTES
Enteroparasites and commensals among children in four peripheral districts of Uberlândia, State of Minas Gerais, Machado ER, Rev Soc Bras Med Trop. 2008 Nov-Dec;41(6):581-5. OPEN ACCESS “The parasites and commensals identified were: Giardia lamblia (27.5%), Entamoeba coli (20.6%), Ascaris lumbricoides (14.4%), Enterobius vermicularis (8.8%), Hymenolepis nana (7.5%), Hymenolepis diminuta (5%), hookworms (3.1%), Trichuris trichiura (2.5%), Endolimax nana (2.5%), Entamoeba hartmanni (2.5%), Strongyloides stercoralis (1.3%), Iodamoeba butschlii (1.3%) and Capillaria hepatica (0.6%). n=160, n=93 infected male/female=2.7/1”
Bacterial, archaeal, and eukaryal diversity in the intestines of Korean people, Nam, Y.-D.et al (2008) The Journal of Microbiology, 46(5), 491–501. Only protozoa identified were Blastocystis. The study only involved TEN subjects….
Waiting for the human intestinal Eukaryotome. , Andersen LO, Vedel Nielsen H, Stensvold CR, ISME J. 2013 Jul; 7(7):1253-5.
Nice commentary piece on the current (2013) state of the eukaryotome.
Gut Protozoa: Friends or Foes of the Human Gut Microbiota?, Magali Chabé et al , Trends in Parasitology, Opinion| Volume 33, ISSUE 12, P925-934, December 01, 2017
An opinion piece. Authors note that gut microbiome studies are almost exclusively focussed on prokaryotes, this due in large part to existing technologies (16S rRNA gene amplification) and a geographic bias to resource-rich Western based gut surveys. The authors state “We argue that protozoa,like helminths, represent an important factor to take into account when studying the gut microbiome, and that their presence – especially considering their long coevolutionary history with humans may be beneficial ” “Here, we argue that some intestinal protozoan inhabitants could play an important, yet largely unrecognized, role in shaping the gut bacterial microbiota and in maintaining the host–microbe equilibrium, and they should be considered as ‘friends’ of the human gut…..Outstanding questions….The gut microbiome in industrialized nations is less diverse than that found in non-industrialized nations. The question: are protozoal and helminth infection/colonization responsible for this higher diversity. And, does a highly diverse gut microbiome confer protection against certain diseases (e.g. Crohn’s disease)”
Are human intestinal eukaryotes beneficial or commensals? Lukeš J., Stensvold C. R., Jirku-Pomajbíková K., Wegener Parfrey L. (2015) PLoS Pathog.11 OPEN ACCESS Human biome ratio: one human cell to ten microbes…they prefer eukaryome to other terms such as eukaryotome.
Blastocystis can be found in 10-100% of individuals in surveys… “Is the eukaryome beneficial overall? We do not know, and clear-cut cases of beneficial eukaryotes in the human gut are few…. Indeed, the fast increase of the autoimmune and inflammatory diseases including Crohn’s disease, ulcerative colitis, various allergies, rheumatic arthritis, and others, are firmly associated with changes in the gut microbiome….Rethinking the Term “Parasite”… The term “ symbiont” encompasses all host-associated organisms across the spectrum of possible relationships (beneficial, detrimental, or neutral)…There is evidence that increased gut microbiome diversity is associated with lower risk of autoimmune disease and inflammatory disease.”
Parasite-Microbiota Interactions With the Vertebrate Gut: Synthesis Through an Ecological Lens, Jacqueline M. Leung, Front Microbiol. 2018; 9: 843. OPEN ACCESS Massive review of much complex material…200 references. The manifold relationships of helminths and protozoa with the bacterial gut microbiome, gut cellular physiology and the immune system…
“Colonization of the gastrointestinal (GI) tract by a parasite markedly alters physical aspects of the gut ecosystem and hence the landscape in which the microbiota reside. Infection can alter epithelial barrier function by affecting mucus production and composition, tight junctions, as well as epithelial cell turnover.”
Microbial eukaryotes in the human microbiome: ecology, evolution, and future directions, Parfrey L. W., Walters W. A., Knight R. (2011). Front. Microbiol. OPEN ACCESS
“Most microbial eukaryotes that reside in the gut do not cause harm, being either beneficial or commensal…While the focus is generally on pathogens (in terms of study effort, genome sequencing, etc.), most microbial eukaryotes that reside in the gut do not cause harm, being either beneficial or commensal. Some eukaryotic microbes are considered probiotics, in particular the yeast Saccharomyces boulardii was originally isolated to combat Cholera, and it now marketed as a cure for diarrhea (McFarland and Bernasconi, 1993). Other eukaryotes have been shown to be beneficial in certain context, for example the hypothesized reduction in asthma and allergies in conjunction with hookworm infection (Falcone and Pritchard, 2005). Many other eukaryotic microbes are present in the gut but do no harm (they are commensals), including Pentatrichomonas and Entamoeba dispar (Bogitsh et al., 2005)….The diversity of microbial eukaryotes within an individual is low, with fewer than 10 phylotypes recovered per individual (Ott et al., 2008; Scanlan and Marchesi, 2008). ….many people with E histolytica or G lamblia are asymptomatic and one estimate is that only10% of E histolytica infections become invasive.”
Communities of microbial eukaryotes in the mammalian gut within the context of environmental eukaryotic diversity. Parfrey LW, Front Microbiol.
2014 Jun 19;5:298.OPEN ACCESS
A very technical paper. “Eukaryotic microbes are common components of the human gut microbiota in healthy individuals. Blastocystis, Entamoeba, trichomonads, and yeast were frequently detected in human gut samples. Closer inspection of the taxa reveals that most are likely commensal rather than pathogens. For example, Entamoeba was detected in both populations. While the genus Entamoeba includes E. histolytica, the causative agent of the deadly amoebic dysentery, the vast majority of Entamoeba sequences detected here fall within the commensal species Entamoeba coli, E. dispar, and E. hartmanni. Parfrey conclusions: Interestingly, humans with non-western diets and lifestyles are comparable to other mammals in the microbial eukaryote diversity they harbor. In contrast, humans living Western lifestyles instead have very low diversity of gut microbial eukaryotes. However, the eukaryotic microbiota of the western population appears depauperate.”
Host-Protozoan Interactions Protect from Mucosal Infections through Activation of the Inflammasome, Chudnovskiy A, et al. Cell. 2016;167(2):444-456.e14. OPEN ACCESS The mammalian gut is host to a wide consortium of microbes from diverse phyla including viruses, prokaryotic bacteria and eukaryotic microbes. The latter, broadly referred to as the eukaryome (Lukes et al., 2015), is comprised of a myriad of fungi, helminths and protists….The impact of these species on the host in general and, in particular, on the immune system has been practically neglected….Controversies are ongoing whether [various protozoans] are commensals, pathobionts, or pathogens of the human intestinal tract (Lukes et al., 2015). Certainly D. fragilis has been identified as an etiological agent of irritable bowel syndrome (IBS) (Stark et al., 2007), but it has also been recognized for its potential protective effect against disease flares in patients with inflammatory bowel disease (IBD)
¶ CONSTIPATION, FECAL TRANSPLANTATION, THE WATER FALLACY AND MISCELLANY
Moreover, the definitions of CC and the more-strictly defined entity functional constipation (FC) have evolved over time. According to the Rome IV criteria,1 FC must include ≥2 of the following symptoms:
(1) Straining during >25% of defecations.
(2) Lumpy or hard stools with > 25% of defecations.
(3) Sensation of incomplete evacuation >25% of the time.
(4) Sensation of anorectal obstruction/blockage > 25% of the time.
(5) Manual maneuvers to facilitate defecation >25% of the time.
(6) Less than 3 bowel movements per week.
Staller quotes a further definition/observation: “Recent normative data from the National Health and Nutrition Examination Survey (NHANES) suggests that normal bowel movement frequency ranges from 3 per day to 3 per week with a
broad range of normal consistency”
Refractory Constipation, What is the Clinician to Do? Kyle Staller, J Clin Gastroenterol 2018
The ROME IV defines constipation as moving your bowels 3 or fewer times per week, incomplete elimination or feeling ‘blocked’ at least 25% of the time. If these resonate with you, you’re not alone – constipation may affect as many as 20% of us. Also, for consideration: North American annual laxative spending: 500 million dollars.
Chronic constipation A review of literature, Mojgan Forootan, MD, Medicine (2018)It is worth noting that there is currently no ideal definition for constipation;….a rather old-fasioned review, though complete. Absolutely no mention of the colonic microbiome.
Zhao Y, Yu YB. Intestinal microbiota and chronic constipation. Springerplus. 2016;5(1):1130. Published 2016 Jul 19. OPEN ACCESS Intriguing description of very small sample size studies of fecal transplantation in the treatment of chronic constipation. “Multiple studies have revealed disturbances in the composition and stability of the gut microbiota in constipated patients compared with healthy controls.”…mentioned in this and several other articles is the difficulty of sampling the ‘mucosal microbiota’ which can be significantly different from the fecal microbiota.”
Fecal microbiota transplantation in patients with slow-transit constipation: A randomized, clinical trial, 2017, Hongliang Tian, PLoS ONE 12(2) OPEN ACCESS endpoint of study: clinical cure: defined as > three complete spontaneous bowel movements per week. N=60. 30 patients in (Fecal Microbiota Transplantation) FMT arm, 30 patients in no tx arm. 30% higher cure rate in the FMT arm. Both Wexner and Bristol metrics were employed in the study. Bristol 1-2 were classed as “hard”, 3-5 as “normal”, and 6-7 as “loose”. This study makes no mention of eukaryotes detected in the stool. The study also did not describe pre and post fecal transplant microbiome profiles of the patients.
Gut microbiota composition associated with stool consistency, Tigchelaar EF et al., Gut 2015;0:1–2. Authors did not find a strong association of Bristol Stool Form Score with microbiome diversity, but there were definite microbiologic ‘compositions’ that varied across the spectrum from very hard to semi-liquid stool.
Water and fluid intake in the prevention and treatment of functional constipation in children and adolescents: is there evidence? , Sabine Nunes Boilesen et al, J Pediatr (Rio J). 2017;93:320—7.
An extensive literature review. The authors conclude that there is ‘no favorable role’ for fluid intake in the relief of constipation. THANK YOU. I’ve been saying this for years. PSYLLIUM is the answer.
Diet and lifestyle rules in chronic constipation in adults: From fantasy to reality, Fathallah N1 Presse Med. 2017 Jan;46(1):23-30. doi: 10.1016/j.lpm.2016.03.019. Epub 2017 Jan 5. Water has no demonstrated benefit in the relief of constipation.DID YOU HEAR ME? PSYLLIUM!
Management of Constipation in Older Adults, Anne Mounsey, Am Fam Physician. 2015 Sep 15;92(6):500-504. No evidence for hydration, water repletion, water drinking in the management of constipation. PSYLLIUM, ! I say.
(Self-) infections with parasites: re-interpretations for the present, Julius Lukeš, Trends in Parasitology, 30 (2014) 377-385. !!Self infection….shades of “the John Hunter’s gonorrhea experiment (possibly apocryphal)….
“Here, we critically review cases in which humans were deliberately infected with parasites. Moreover, we summarize the contribution of (self-) infections and propose protist and helminth candidates, chosen on the basis of several criteria, to test as possible therapy for selected human diseases. ” Lukeš cites Despommier’s 1995 book, Entamoeba histolytica for the history of Schaudinn’s death at 35 years of age, due to self-infection with E histolytica, in an attempt to differentiate it from E dispar…. This article contains a long list of human auto-experimentation with a variety of protists and helminths, and in part makes rather discomfiting reading. Lukeš lists E hartmanni as a possible candidate for therapy of human immune-mediated disorders.
Gut Microbiota and Chronic Constipation: A Review and Update, Ohkusa T et al, Front Med (Lausanne). 2019 Feb 12;6:19. 2019. OPEN ACCESS
Conclusions: Evidence indicates that dysbiosis of gut microbiota may contribute to functional constipation and constipation-type irritable bowel syndrome.
WEXNER CONSTIPATION SCORE
from: A constipation scoring system to simplify evaluation and management of constipated patients, Agachan, F et al, Dis Colon Rectum. 1996 Jun;39(6):681-5. A score of 30 is CONSTIPATED
1-2x per 1-2 days 0
Difficulty: painful evac
Completeness: Feeling of incomplete evac
Pain: Abd Pain
Time: Minutes in lavatory/attempt
stimulative laxatives 1
digital assist or enema 2
Failure: Unsuccessful attempts for evac/24hr
History: years of constipation
(Minimum Score, 0; Maximum Score, 30)
¶ TERMINAL CURIOSITIES
Came across two ‘martyred’ parasitologists while researching this TWiP episode: Prowazek and Schaudinn. I believe that Dr Despommier’s 1995 book Entamoeba histolitica details the death of Schaudinn. Perhaps a new section of heros and martyrs (and maybe self-experimenters) can be shoe-horned in sometime.
Biographical notes: Max Hartmann (1876-1962):
Worked with Chagas at the Instituto Oswaldo Cruz (IOC) from May-Nov 1909 where they co-authored several papers on free-living protozoa. Other German scientists at the IOC during this time were Stanislaus von Prowazek† (1875-1915) and Gustav Giemsa (1867-1948).
Hartmann’s career began at the Königlischen Institut für Infektionskrankheiten (to be renamed the Robert Koch Institute). In 1935 was the director of protozoology at the Institute für Biologie in Berlin-Dahem. Hartmann was also a theoretical biologist and was primarily interested in general theories of sexuality and sexual reproduction.
† Prowazek, who collaborated with Henrique Rocha Lima (1879-1956) on discovery of the causative organism of typhus. Prowazek died at age 40 during his research on typhus in German prisons. He was honored by Rocha Lima, who eponymously named the epidemic typhus organism Rickettsia prowazeki.
Die Sexualitätstheorie und “Theoretische Biologie” von Max Hartmann in der ersten Hälfte des zwanzigsten Jahrhunderts by Heng‐an Chen Review by: rev. by Marsha L. Richmond, Isis, Vol. 96, No. 1 (March 2005), p. 126
Some biographical information on Max Hartmann here
Isis, Vol. 96, No. 1 (March 2005), p. 126 on file /downloaded from JSTOR 02/28/19
Huge bio of Max Hartmann here.
Nature, August 24, 1946, No.4008, p265, News clip.
Acknowledging Max Hartmann’s 70th birthday: Mentioned is his well respected textbook Allgemeine Biologie, at that time in its third edition. Also noted: “Dr Hartmann was a fearless and outspoken critic of Nazism.”
Scatologic Rites of All Nations, A Dissertation upon the Employment of Excrementitious Remedial Agents in Religion, Therapeutics, Divination, Witchcraft, Love-Philtres, etc., in all Parts of the Globe. Captain John G Bourke Washington DC: W H Lowdermilk & Co, 1891. Clearly subtitled: NOT FOR GENERAL PERUSAL (OPEN ACCESS, download available at archive.org) This book is a must browse for anyone interested in ‘all things fecal’. I cannot recommend it enough!
Scatomancy, kleptoparasitic dung beetles (in wikipedia), as used in divination by the ancient Egyptians… This is where I learned the word kleptoparasitic. It is a super-word.
The mythology of water as a cathartic. I have a few references on this in the constipation references. This spurious belief should be appended to Browne’s Pseudoxia epidemica.
Sexually transmitted amoebiasis, Patricia Morán, et al, Am J Trop Med Hyg. 2013 Jan 9; 88(1): 186–190. OPEN ACCESS For Dr Racaniello, whose thorough clinical history always includes the important but delicate questions. Case report of two cases, where both male patients had significant genital ulceration. Note: photographs of lesions not for the faint of heart.
RE: Comment in TWiP 166 that Joseph Merrick aka ‘The Elephant Man’ suffered from neurofibromatosis.
Though I generally detest historical medical speculation (e.g. Van Gogh had macular degeneration….King George had porphyria, etc etc. ) I am moved to comment RE: The Elephant Man (Joseph Merrick †1890) In 1986 it was conjectured that he had Proteus syndrome. DNA tests on his hair and bones in a 2003 study were inconclusive.
Clinical and historical aspects of the Elephant Man: Exploring the facts and the myths, Catherine Huntley et al, Gene 555 (2015) 63–65.
When I heard the case of the 30 year old woman with Entamoeba hartmanni, I was reminded of the difficulty in distinguishing Entamoeba hartmanni from dwarf forms of Entamoeba histolytica. There are some clear differences in the appearance of the peripheral chromatin in the nucleus as well as the appearance of the karyosome, but careful examination of properly stained smears must be done to distinguish the two.
There is also an overlap in the size of the cyst stage of E. hartmanni and dwarf E. histolytica.
Since the lady in question has no “symptoms” except for normal bowel habits after having problems with constipation, maybe she has a mild form of Entamoeba histolytica infection, and the organism was erroneously called Entamoeba hartmanni. The literature does say that only some people infected with E. histolytica develope amoebic dysentery.
There are other differences in the cyst and trophozoite forms of these organisms but they require a properly stained smear of the concentrated specimen.
Also Entamoeba histolytica and Giardia are the most common parasites acquired in the Dominican Republic.
I hope I’m not offending anyone by the above observation. Being a laboratory scientist, I understand the difficulties of performing these tests.
Thanks very much for sharing your knowledge with your listeners! I have learned so much from you!
Cecelia from St. Petersburg, Fl
PS. My husband just returned from a yearly medical mission trip in the DR.
Delighted to have won the book from TWiP 166.
As for the case from the latest podcast…
Entaemoeba hartmanni is a non-pathogenic colonic protozoan. It is a reflection that an individual has ingested contaminated water or food or has suboptimal hygiene practices.
Found on its own in an asymptomatic patient it requires no intervention, and if found in a patient with diarrhoea should prompt further investigations to search for a pathogenic organism that has been overlooked.
There are lots of other non-pathogenic gut protozoa which often get picked up on in stools, and our tropical advice service frequently gets contacted to ask if treatment is required for a number of organisms.
A non-exhaustive list includes:
- Entamoeba’s Coli, Dispar, Moshkovskii
- Endolimax nana
- Iodamoeba Buetschlii
The primary care physician may or may not have offered treatment with metronidazole, but reassurance would be all that was necessary.
I am wondering if her time spent in DRC lead to a change in gut flora and a resulting shorter transit time..?
From a brief search of the literature it seems that gut microbiota plays an important, but as yet not fully elucidated, role in intestinal motility (1). And that you can slow gut transit time by transplanting the gut microbiota from individuals with constipation into mice (2)! Faecal microbiota transplantation has already shown its utility in the treatment of refractory C.difficile infection, so maybe it can be a cure for constipation as well as diarrhoea in the future..? The gut microbiome is a fascinating subject that I believe we are only just beginning to gain an understanding of.
Additionally, thank-you Dickson for sharing your trials and tribulations of long-distance air travel. I too find it to have the same effect.
Is the diarrhea associated with giardia all due to the malabsorption of fat? If so, would an infection in a vegan on a low fat diet be asymptomatic?
Thank you for keeping me entertained whilst on my sick bed … 4 months later still recovering from a prolapsed disc L5 and separated from reaching my scientific dreams (PhD and beyond), but you’ve raised a smile from me.
Some years ago, I did tech support. One user insisted on being present when I worked on their computer. We’d arranged for a 4pm appointment. On arriving, I was asked “How long is this going to take? I have to go home.” By the look on their face, the person appeared to be in some sort of distress.
“What’s the matter?”
“I have to go to the bathroom.”
“But the men’s room is just down the hall.”
“I don’t use public restrooms. Flushing the toilet sends a fine spray of feces onto the seat.”
I remembered this when hearing the remarks on TWiV 167 about fecal-oral transmission. Was feces actually aersolized by flushing? Indeed there is “toilet plume.”
Pervasive and invisible contamination is possible.